الفهرس | Only 14 pages are availabe for public view |
Abstract This study describes spectrophotometric and fluorimetric methods for the analysis of five therapeutically important and widely used calcium channel antagonist drugs. These drugs are nifedipine (NIF), nicardipine hydrochloride (NIC), nimodipine (NIM), felodipine (FEL) and amlodipine besylate (AML). The drawbacks encountered in the analytical methods reported in literatures for the analysis of these drugs were our interest in selection of these drugs to be the target of this study. In this thesis sevsral analytical methods have been developed for the determination of 1, 4-DHP. The developed methods are classified into general and selective methods. 1. GENERAL METHODS 1.1. Oxidation Methods Two oxidation spectrophotometric methods and one fluorometric method were developed and validated for determination of the investigated drugs via oxidation with potassium permanganate and ceric ( IV) ammonium sulphate in acidic medium. 1.1.1. Using Potassium Permanganate in acid medium Our present work is a new study for assay 1, 4-DHP drugs in acidic medium using KMnO4. It is an oxidation-based spectrophotometric method which was applied and validated for determination of 1, 4-DHP drugs via their oxidation with potassium permanganate in sulphuric acid. The concentrations of the drugs in their samples were determined by measuring the decrease in the absorption intensity of the pink colour of permanganate at 525 nm. Different variables which affected the reaction conditions were carefully studied and optimized for each investigated drugs. English summary and conclusion 114499 1.1.2. Using Ce (IV) in acid medium (Spectrophotometrically) Ce (IV) was used before for determination of NIF, NIM and FEL as titrimetric method using ferroin indicator or spectrophotomerically with NIM through direct measurement of produced cerium (III), spectrofluorometric with NIF and Kinetic spectrofluorometric with NIC. Our present work is a new assay of 1, 4-DHP drugs using p-DMAB as a second reagent for determination the excess Ce (IV). It is an oxidation-based spectrophotometric method which was applied and validated for determination of 1, 4-DHP drugs via their oxidation with Ce (IV) in perchloric acid and measuring the difference in the absorption intensity (ΔA) at 464 nm. Different variables affecting the reaction conditions were carefully studied and optimized for each investigated drugs. 1.1.3. Using Ce (IV) in acid medium (Spectrofluorometrically) The aim of the present study was directed to the development of new simple spectrofluorimetric method for analysis of drugs in pharmaceutical dosage forms. It is an oxidation-based direct spectrofluorometric method which was applied and validated for determination of 1, 4-DHP drugs via their oxidation with Ce (IV) in sulphuric acid and direct monitoring the fluorescence of the produced cerium (III) at 355 nm (excitation at 255 nm) which proportional with the concentrations of the drugs in their samples. Different variables affecting the reaction conditions were carefully studied and optimized for each investigated drugs. 1.2. Bromination and Coupling Method Using NBS and INC, PAP This part describes a spectrophotometric method for determination of all the 1, 4-DHP through their bromination of the active methylene group with Nbromosuccinimide (NBS) reagent and subsequent treatment of the residual NBS with indigo carmine (INC) and p-aminophenol (PAP) as dyestuffs. The formed coloured products were measured spectrophotomerically at 607 and 556 nm for NBS/INC and NBS/PAP method respectively. The method was applied before on some 1, 4-DHP English summary and conclusion 115500 drugs using bromate-bromide mixture and our present work is a continuation of the previous study for application on 1, 4-DHP drugs in different conditions using other more safe reagents rather than BrO3 - / Br- mixture. Different variables affecting the reaction conditions were carefully studied and optimized for each particular reagent (chromogenic or conditioning) with all the investigated drugs. 2. SELECTIVE METHODS The previous methods are considered as general non-selective methods for quantification of all the studied 1, 4-DHP drugs. In searching for selectivity some nucleophilic reagents were tried successfully in this field where they could be applied only for 1, 4-DHP drugs that contain either active methylene group which attached with dihyDROPyridine ring or basic center (forming ion pair complex) or nitro group which can be reduced to aromatic primary amine. 2.1. Vanillin Method A new simple and specific spectrophotometric method, which is developed for the determination of the studied drugs by reaction with vanillin in presence of conc. hydrochloric acid. The method depends on the interaction of the active methylene group exist in a drug molecule with vanillin which results in the formation of coloured substituted product. The increase in the absorption intensity was measured at 500 nm for NIF, NIC, NIM, FEL and 479 nm for AML. A study for all variables was carried out to optimize the reaction conditions. A validation study for the proposed procedure according to USP 2002 was also performed. English summary and conclusion 115511 2.2. Tetrabutylammonium hydroxide Method While the 1, 4-DHP drugs are mostly behave as weak acids thus upon treatment with strong bases they afford the corresponding anions and appreciable red shift occur. So; the addition of TBAH base to all 1, 4-DHP drugs in dimethylsulphoxide (DMSO) produces a pronounced bathochromic effect; which is due to anion formation in the basic medium utilizing the proton in 1, 4-DHP ring. Different variables affecting the reaction conditions (type of base and the organic solvent) were carefully studied and optimized with the investigated drugs 2.3. Non-Extractive Ion-Pair Formation Method Using eosin Y This study describes a generic non-extractive spectrophotometric procedure for determination of NIC and AML by formation of coloured ion-pair complexes with eosin Y reagent in buffered medium using methylcellulose as surfactant. The formed ion-pair complexes were measured spectrophotomerically at 549 nm. Different variables affecting the reaction conditions were carefully studied and optimized for each particular parameter with the investigated drugs. 2.4. Schiff’s base Method Using p-DMAB reagent This method was applied before for determination of NIM. And in this study a continuation of the previous one for the determination of NIF and NIC; containing nitro group. which were reduced with Zn0/HCl mixture then react with p-DMAB to form Schiff’s base. This reaction yielded a coloured reaction product which can be measured at 434 and 441 nm for NIF and NIC respectively. Different variables affecting the reaction conditions were carefully studied and optimized for particular reagent with NIF and NIC. |